Convergence Science combines concepts and technologies from multiple fields. Our program relies on expertise from engineers, chemists, computer scientists, biologists, immunologists and medical doctors, working together to transform the way we think of brain tumor therapy.
In close collaboration with the Division of Neurotechnology within the Department of Neurosurgery, we are working on the following projects:
- Focused Ultrasound. Brain Tumor Center scientists develop innovative focused ultrasound (FUS) technologies. These include sonodelivery technologies for enhancing therapeutic delivery for the treatment of brain tumors; sonobiopsy technologies to identify biomarkers for the early diagnosis of brain cancers; and sonogenetics technologies for understanding brain function.
- Laser-based surgery. MRI-guided laser interstitial thermal therapy (LITT) employs advanced MR imaging and a laser to target and use heat to ablate brain tumors that lie deep within the brain that cannot be accessed by traditional surgical techniques. This highly targeted therapy minimizes harm to surrounding brain tissue, which allows the patient to recover in a much shorter time than open brain surgery. Our team performed the first FDA-approved laser procedure in brain and currently develops next-generation laser technologies to explore how this surgical tool can be used to improve existing chemo- and immunotherapies. In addition to the effects of LITT on the tumor and the immune system (see our immunotherapy program), we discovered that LITT regionally opens the blood-brain barrier, allowing entry of agents that do not usually pass through the blood-brain-barrier to gain access to the brain tumor. We are currently testing a variety of anti-cancer compounds approved for human use in preclinical models and are discovering significant synergies with laser ablation. Based on results from these preclinical studies, we will design and roll out clinical trials that will bring these novel combinatorial treatments to patients to become the first center to use LITT combined with precision agents selected for an individual tumor’s genetic and epigenetic fingerprint.
- Advanced Brain Mapping. Neurosurgeons often have only limited insight into what cognitive functions may be compromised by the operative procedure. To this end, our surgical team uses advanced functional MRI (fMRI) to map, at unprecedented resolution, motor, sensory, and cognitive functions. These maps then can be easily viewed together with anatomical information as the surgeon plans the operative approach prior to surgery and makes ongoing surgical decisions during the resection. Our team develops these technologies to guide numerous types of therapeutic interventions to improve cognitive outcomes and decrease morbidity after brain tumor surgery.
Nanotechnology enables new ways to diagnose and treat cancer. Nanomedicines can increase payload concentration at the disease site, reduce toxicity and enhance therapeutic effect compared to drugs in their “free” form.
Research by our team has been focused on the preclinical and clinical development of a nanotechnological platform, termed Spherical Nucleic Acids (SNAs). SNAs consist of a nanoparticle core densely functionalized with a shell of radially oriented synthetic oligonucleotides. The unique three-dimensional architecture of SNAs enables robust uptake into tumor and immune cells. Current efforts are focused on the preclinical and clinical development of next-generation SNA platforms for gene regulation, the activation of innate immunity and cancer vaccination.
- Gene regulation. When composed of gene-regulatory small interfering (si)RNA, SNAs silence gene expression and induce immune responses superior to those raised by the oligonucleotides in their “free” form. Early phase clinical trials of gene-regulatory siRNA-based SNAs in glioblastoma (NCT03020017) have shown that SNAs represent a safe, brain-penetrant therapy for inhibiting oncogene expression in brain tumors. Ongoing efforts are optimizing first-generation SNAs for more effective gene regulation in tumor cells and cells in the tumor microenvironment.
- Immunotherapy. Our team is developing next-generation SNA architectures for potent activation of innate immunity, by engaging pattern recognition receptors and DNA sensors. Exciting preclinical data demonstrate potent immunostimulatory activity of these architectures. We are planning unique early phase clinical trials to test their immunostimulatory effects in brain tumor patients.
- Cancer vaccines. Immunostimulatory SNAs can be co-functionalized with peptide antigens to activate antigen-presenting and tumor-targeting effector T cells. Our team develops SNAs which are conjugated with oligonucleotides (i.e., ‘adjuvants’ to increase the innate immune response to the antigen within APCs). The oligonucleotides, in turn, are coupled to model peptides derived from tumor-associated antigens via specific linker chemistries.
- High-throughput screening and artificial intelligence for nanotherapeutic drug development. It is now well-established that structure makes a significant difference in nanotherapeutic performance. However, the vast design spaces available for SNAs and other types of related nanomaterials necessitate advanced methods for nanodrug development. Our team through collaboration with Northwestern University is utilizing high-throughput methods for synthesizing and evaluating construct activity. Empirical high-throughput experimentation data are used to train non-linear machine learning algorithms to predict activity from nanoconstruct properties. We are developing a pipeline for the systematic, large-scale evaluation of structural features contributing to nanoarchitecturepotency.